tbuckley/cabot-search huggingface dataset:
Abstract 13860: Heart Failure With Preserved Ejection Fraction Induced by Amyloid Light Chain Amyloidosis: A Case Report
Authors: Juan R Fondeur Acosta, Danna Reyes, Annie Gisselle Ramirez
Journal: Circulation (2022)

Introduction: Cardiac amyloidosis is a clinical disorder defined as an extracellular deposition of protein in the heart. Typically, signs and symptoms of heart failure develop in the advanced disease. High index of suspicion is required for the diagnosis of this disorder. Results: A 62 years old male came to the cardiology clinic due to lower extremity edema, fatigue, dyspnea on exertion. He had a 3 month history of progressive lower leg edema. On physical examination he had a positive S4; lung sounds were diminished and there was dullness to percussion over the lower two thirds; and bilateral lower extremity edema. Hospital admission was decided for management of decompensated heart failure. On admission, the surface ECG showed normal sinus rhythm with low QRS voltage in the limb leads, a RBBB and LPFB. Initial laboratory reported elevated NT-proBNP: 13,816 pg/mL. Chest x-ray demonstrated right interstitial infiltration and bilateral pleural effusion. The echocardiogram revealed severe concentric hypertrophy of the left ventricle, an apical sparing left ventricle longitudinal strain, and an ejection fraction of 68%. A cardiac MRI showed concentric biventricular hypertrophy associated with extensive diffuse late gadolinium enhancement, suggestive of cardiac amyloidosis. Screening resulted in a Perugini score of 1 on Tc-PYP scintigraphy, elevated Kappa and Lambda light chains on serum, and kidney biopsy positive for amyloidosis. Hematology-oncology consultation was done and a daratumumab-CyBorD protocol was started. Conclusions: This case elucidated a stepwise diagnostic approach of cardiac amyloidosis in a patient presenting with signs and symptoms of heart failure. Amyloid AL cardiac amyloidosis and its repercussions are severe because it not only compromises by being infiltrative but also by its toxic capacity. A high index of suspicion and a multidisciplinary approach is needed in order to improve quality of life and prolong survival.
Abstract 12921: National Trends and Sex Differences in Adults &lt; 35 Years Old With Acute Myocardial Infarction in the United States From 2010 - 2018
Authors: Sara J King, Rajiv C Patel, Sameer Arora, Sidney C Smith, George A Stouffer
Journal: Circulation (2022)

Introduction: Few studies have examined acute myocardial infarction (AMI) trends among adults &lt; 35 years old. We analyzed hospitalization and mortality trends, risk factors, and sex differences among patients &lt; 35 years old with AMI. Methods: We queried the National Readmissions Database (NRD) for all hospitalizations from 2010 to 2018 aged 20-34 with a principal diagnosis of AMI. We assessed the annual trend in AMI hospitalization rates and in-hospital mortality using linear regression, stratifying by sex. We analyzed procedures and risk factors both overall and by sex, and performed bivariate analyses using chi-square to compare sex differences. All frequencies were weighted to reflect national estimates provided by the NRD. Results: A total of 40,209 AMI hospitalizations in individuals &lt; 35 years old were identified from 2010 to 2018. Hospitalization rates were higher in men as compared with women (9.6/100,000 vs. 4.0/100,000, p &lt; 0.05) and remained stable for men while there was a trend towards increasing hospitalization rates for women (Figure, p = 0.06). Women were more likely to be hypertensive, diabetic, and obese, while men were more likely to have hyperlipidemia and a history of tobacco or cocaine use (all p &lt; 0.01). The rate of obesity increased over time for both men and women while rates of hypertension and diabetes increased only for women (all p &lt; 0.05). As compared with men, women were less likely to get PCI (47.8% vs. 54.9%, p &lt; 0.01) but in-hospital mortality rates were similar (2.22% vs. 1.60%, p = 0.29). Conclusions: Among those &lt; 35 years old with AMI, women were more likely to be hypertensive, diabetic, and obese, with increasing prevalence, while men were more likely to have hyperlipidemia and a history of tobacco or cocaine use. Hospitalization rates for AMI were higher in men and there was a significantly higher use of PCI in men compared to women although in-hospital mortality rates were similar.
Abstract 126: The Association Of Higher Or Lower Mean Arterial Pressure On Kidney Function After Cardiac Arrest: A Post-hoc Analysis Of The Comacare And Neuroprotect Trials
Authors: Johanna Laurikkala, Koen Ameloot, Matti Reinikainen, Pieter-Jan Palmers, Eline Bogaerts, Cathy De Deyne, Ferdinande Bert, Matthias Dupont, Stefan P Janssens, Joseph Dens, Johanna Hastbacka, Pekka Jakkula, Pekka Loisa, Thomas Birkelund, Erika Wilkman, Suvi Vaara, Markus B Skrifvars
Journal: Circulation (2022)

Introduction: Acute kidney injury (AKI) denotes a sudden reduction in kidney function manifested by a rise in S-creatine levels and reduced urine output. Studies have suggested an association between AKI severity and outcomes after OHCA. Various criteria have been used to define AKI, the Kidney Disease Improving Global Outcomes (KDIGO) published in 2012 being the currently used tool. AKI is a feature of post-cardiac arrest syndrome.During post-CA syndrome, possible causes of renal damage are direct renal ischaemic-reperfusion injury and indirect renal damage characterized by the activation of inflammatory and coagulation pathways. Although the overall mortality rate after CA mainly relates to hypoxic-ischaemic brain injury, damage to other organs also has prognostic implications. Methods: Pooled post-hoc analysis of the COMACARE (NCT02698917) and NEUROPROTECT (NCT02541591) trials that randomized patients to lower (MAP 65-70 mmHg) or higher (MAP 80-100 mmHg) targets for the first 36 hours of post-CA intensive care. Kidney function was categorised using the KDIGO classification during the first five days after OHCA. We used Cox regression analysis to identify factors associated with AKI after OHCA. Results: A total of 227 patients were included: 115 in the high MAP group and 112 in the low MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 (47%) patients had AKI in the high MAP group and 46 (54%) in the low MAP group (p = 0.51). The mean creatinine and mean daily diuresis were 104 (95% CI 94-115) μmol/l and 1989 (95% CI 1829-2150) mL/day in the high MAP group and 111 (95% CI 99-122) μmol/l and 1677 (95% CI 1530-1824) mL/day in the low MAP group. In a Cox regression model, independent AKI predictors were previous hypertension (HR 1.72; 95% CI 1.07-2.78; p = 0.03), bystander cardiopulmonary resuscitation (hazard ratio [HR] 0.46; 95% CI 0.29-0.73; p &lt; 0.01), shockable initial rhythm (HR 0.36; 95% CI 0.21-0.61; p ≤ 0.01), and time to ROSC (HR 1.04; 95% CI 1.02-1.06; p &lt; 0.01) whereas high/low MAP was not an independent predictor of AKI. Conclusions: KDIGO1-staged AKI is common after CA and is associated with previous hypertension and CA factors. Targeting higher MAP after CA does not appear to influence the development of AKI.
Abstract 11314: Essential and Evidence-Based Cardiovascular Disease Medicine Availability in Low-Cost Generic Drug Plans
Authors: Ivy Ton, Towhid Rahman, Jungyeon Moon, Cynthia Jackevicius
Journal: Circulation (2022)

Introduction: Patients’ lack of access to affordable cardiovascular disease (CVD) medicines poses a crucial barrier to achieving desired cardiovascular outcomes. Many pharmacies have launched low-cost generic programs (LCGP) to expand medication accessibility. It is uncertain whether LCGPs include CVD drugs recommended by World Health Organization Essential Medicines List (WHO EML) and promote evidence-based prescribing. Our study aimed to estimate the availability of essential and guideline-recommended CVD medicines on LCGP in the United States (US). Methods: We selected 6 CVD conditions: atrial fibrillation (AF), heart failure (HF), hyperlipidemia (HLD), hypertension (HTN), stable angina (SA), and secondary prevention (SPX). LCGPs in the US with publicly available formularies were identified in February 2022. We used the 22 nd WHO EML edition and Class 1A recommendations (1ARec) from current CVD guidelines as reference standards. Availability was estimated using the proportion of coverage for each LCGP overall, and by condition. Results: Nineteen LCGPs were included. There were 122 WHO EML and 155 1ARec CVD drugs. No LCGPs offered at least 50% of WHO EML and 1ARec. Both WHO EML and 1ARec analyses showed that 9 of 19 LCGPs covered at least 30% of listed medications. Out of the 19 LCGPs, the proportion of essential and evidence-based CVD medicine availability was highest at Kroger (46.3% and 47.9%) and lowest at Costco (5.0% and 6.1%), respectively. Higher availability was observed for HLD medications: only TOPS and the Mark Cuban Plan had at least 80% of WHO EML available, and only the Mark Cuban Plan had at least 80% of 1ARec medications covered. HTN drugs were least available for both. Conclusion: The accessibility of CVD medicines is low in LCGP formularies with variation in availability by pharmacy and condition. To optimize the accessibility of CVD medicines and health outcomes, pharmacies with LCGPs should offer more essential and evidence-based CVD medicines.
Abstract 13977: The Impact of Left Atrial Functional Changes on Clinical Outcomes Following Transcatheter Aortic Valve Replacement
Authors: Sahrai Saeed, Carlo Mannina, Sushmita Ramanujam, Gregory Gibson, Harminder Gill, Omar Chehab, Karine Grigoryan, Jane Hancock, Tiffany Patterson, Steven A Niederer, Simon R Redwood, Bernard Prendergast, Ronak Rajani
Journal: Circulation (2022)

Background: In patients with aortic stenosis (AS) and preserved left ventricular (LV) function, pre-intervention left atrial (LA) enlargement is common and predicts adverse events. Changes in LA function are appropriate markers of LV response to AS but have not been well explored in patients undergoing TAVI. The objectives of the current study were to evaluate changes in LA function following TAVI and their impact upon clinical outcomes. Methods: A total of 313 consecutive patients undergoing TAVI were included. There were 160 (51%) paired echocardiographic datasets with a median time of 1 (range 0-57) days pre-TAVI and a median time of 120 (1.2-810) days post-TAVI. All studies were evaluated for LA maximum volume index (LAVI max ), LA minimum volume index (LAVI min ), total emptying volume (LAEV), total emptying fraction (LAEF) and expansion index (LAEI). The pre-defined endpoints were cardiac-related hospitalization and all-cause death. Results: During a mean follow-up of 18 (±9.7) months, there were 58 deaths (18.5%) and 35 (11.2%) hospitalizations for heart failure, whereas 9 (2.9%) patients continued to report symptoms (NYHA 3). The prevalence of atrial fibrillation was 16.3% and coronary artery disease 52.7%. In a multivariate cox regression analysis, lower body surface area (HR 3.79; 95% CI 1.07-13.33, p=0.038), higher serum creatinine (HR 1.004; 95% CI 1.002-1.006, p&lt;0.001) and LV ejection fraction (EF) &lt;50% (HR 1.94; 95% CI 1.08-3.48, p=0.027) were predictors of all-cause mortality, independent of age, aortic valve area, the presence of coronary artery disease and time from index echocardiography to TAVI procedure. All LA function parameters demonstrated an improvement following TAVI (Fig. 1). In univariate cox regression analyses, baseline LA functional parameters were not associated with all-cause mortality alone or a composite of all-cause mortality and cardiac related hospitalization. Conclusions: In patients undergoing TAVI, lower body surface area, higher serum creatinine and LVEF &lt;50% were independent predictors of all-cause mortality. TAVI led to successful reverse LA functional and structural remodeling and LV functional recovery. However, pre-TAVI LA functional and structural parameters were not predictors of survival.
Abstract 12404: Assessment Of Associations Between Hypoglycemia And Cardiovascular Outcomes In The Randomized CARMELINA And CAROLINA Trials Of The Antihyperglycemic Medication Linagliptin
Authors: Ahmed A Kolkailah, Nikolaus Marx, Julio Rosenstock, Odd Erik Johansen, Mark E Cooper, John H Alexander, Robert Toto, Christoph Wanner, Mark A Espeland, Michaela Mattheus, Sven Schnaidt, Vlado Perkovic, Nicholas D Gollop, Darren K McGuire
Journal: Circulation (2022)

Introduction: Bidirectional associations between hypoglycemia and cardiovascular (CV) outcomes were evaluated in 2 CV outcome trials of the DPP-4 inhibitor, linagliptin. Methods: CARMELINA and CAROLINA trials evaluated CV outcomes with linagliptin vs placebo or glimepiride, respectively, in adults with type 2 DM at high CV ± kidney risk; of the 2, CARMELINA was longer duration/higher risk cohort. The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3P-MACE), with heart failure (HHF) added to the primary outcome for the present analyses. Hypoglycemia was defined as plasma glucose &lt;54 mg/dL; severe hypoglycemia defined as needing external help. Associations between the first hypoglycemic episode and subsequent CV events, and conversely, between non-fatal CV events (MI, stroke, HHF) and subsequent hypoglycemic episodes, were assessed using multivariable Cox proportional hazards models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode. Results: In CARMELINA, there was an association between hypoglycemia and subsequent 3P-MACE + HHF (adjusted HR: 1.23; 95% CI 1.04-1.46), and between non-fatal CV events and subsequent hypoglycemia (adjusted HR: 1.39; 95% CI 1.06-1.83). In CAROLINA, there was no significant association between hypoglycemia and subsequent 3P-MACE + HHF (adjusted HR: 1.00; 95% CI 0.76-1.32), nor between non-fatal CV events and subsequent hypoglycemia (adjusted HR: 1.44; 95% CI 0.96-2.16) (Fig). In analyses of CV events occurring within 60 days after hypoglycemia, in both trials, there was either no association observed or too few events to analyze. Conclusion: The observed bidirectional associations between hypoglycemia and CV outcomes in CARMELINA and no significant associations in CAROLINA challenge the notion that hypoglycemia causes adverse CV events, but rather suggest that both hypoglycemia and CV events identify vulnerable patients at risk for both.
Abstract 12334: A Systematic Review and Meta-analysis Curriculum for Internal Medicine Residents Interested in Cardiology
Authors: Zain Ul Abideen Asad, Jessica Reese, Shari Clifton, Shouvik Chakrabarty, Michael Bronze, Chittur A Sivaram
Journal: Circulation (2022)

Introduction: Internal Medicine (IM) residents face major challenges in conducting original research due to inadequate instruction in research methodology and lack of mentorship during the traditional research electives offered during residency. Hypothesis: A novel systematic review curriculum (SRC) can improve resident satisfaction and research productivity. Methods: 8 IM residents interested in cardiology were selected to participate in a 4-week elective focused on conducting systematic reviews and meta-analyses. Didactic lectures, online tutorials, and problem-based exercises were delivered by a multidisciplinary team of educators including a clinical researcher, librarian, and biostatistician. Results: Demographics are presented (Table 1). As compared to 16 residents that underwent traditional research electives, the SRC participants reported higher satisfaction, completed a mentored research project within 4 weeks, presented 4 posters at AHA annual meeting 2020, and finished manuscripts for publication (Figure 1). Conclusions: A focused research curriculum delivered by multidisciplinary educators is better than a traditional research elective and improves resident satisfaction.
Abstract 12324: Biomarker Trends in Patients With Immune-Checkpoint Inhibitor Myocarditis
Authors: Alexi Vasbinder, YeeAnn Chen, Allison Gradone, Tariq Azam, Daniel Perry, Husam Shadid, Elizabeth Anderson, Tonimarie Catalan, Pennelope Blakely, Sarah Adie, Kristen Pogue, Monika Leja, Sarah Yentz, Bryan Schneider, Leslie Fecher, Christopher D Lao, Salim Hayek
Journal: Circulation (2022)

Introduction: Immune checkpoint inhibitors (ICIs) are associated with myocarditis; however, there is no consensus on strategies to identify or monitor for myocarditis. We sought to characterize longitudinal biomarkers in patients receiving ICIs. Methods: We conducted an observational cohort study of adult (≥18 years) patients who had received at least one dose of single or dual ICI at Michigan Medicine between June 2014 - December 2021. Patients were identified as having myocarditis if a clinical diagnosis was noted in the medical record by the cardiovascular consult team. Laboratory values (i.e., high-sensitivity troponin-T [hsTnT], aspartate transaminase [AST], alanine transaminase [ALT], lactate dehydrogenase [LDH], and creatinine phosphokinase [CPK]) were collected from medical records for 12 months after beginning ICI. Results: In 2,606 patients (mean (SD) age 64 (13) years; 60.8% male), 27 (1.0%) developed myocarditis at a median (IQR) time of 28 (18,40) days after starting ICIs. At diagnosis, most patients with myocarditis had a non-cardiac immune-related adverse event (88.9%) and an elevated ALT (88.9%), AST (85.2%), CPK (88.9%), and LDH (92.6%). All patients with myocarditis had an elevated hsTnT. Compared to patients without myocarditis, patients with myocarditis had significant elevations in ALT, AST, CPK, and LDH after starting ICIs (all P&lt;0.001) (Figure). In patients with myocarditis, average concentrations of AST and ALT remained elevated at 12 months, whereas CPK peaked at 1 month then rapidly declined. Average concentrations of all biomarkers in patients without myocarditis were in the normal range. CPK values greater than the upper limit of normal had a sensitivity and specificity of detecting myocarditis of 99% and 23%, respectively. Conclusions: Myocarditis rarely occurs in the absence of other immune-related adverse events. Elevated AST, ALT and CPK should prompt measuring hs-TnT and initiating further evaluation for ICI myocarditis.
Abstract 12025: Fatty Acid-Binding Proteins Promote Pulmonary Arterial Hypertension via Upregulation of Endothelial Glycolysis
Authors: Bin Liu, Shuai Li, Dan Yi, Jiakai Pan, Karina Ramirez, Rebecca Vanderpool, Ruslan Rafikov, Haiwei Gu, Michael Fallon, Zhiyu Dai
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: We hypothesis that endothelial fatty acid metabolism is critical for obstructive vascular remodeling in the pathogenesis of PAH. Methods: A severe mouse model of PH Egln1 Tie2Cre mice were bred with Fabp45 -/- mice to generate Egln1 Tie2Cre / Fabp45 -/- mice. Single-cell RNA sequencing (scRNA-seq) analysis and metabolomic analysis were used to profile the pulmonary cells in Egln1 Tie2Cre mice and Egln1 Tie2Cre / Fabp45 -/- mice. Human hPAEC from idiopathic PAH patients and healthy donors, monocrotaline (MCT)-induced and Sugen5416/hypoxia (SuHx)-induced PH rats were used to measure fatty acid-binding protein 4 and 5 (FABP4 and FABP5) expression. siRNA mediated knockdown of FABP4 and FABP5 and lentivirus mediated FABP4 and 5 overexpression were performed to study cell proliferation, apoptosis, glycolysis, fatty acid oxidation. Echocardiography, hemodynamics, histological and immunostaining assay were performed to evaluate the PH phenotypes. Results: Both FABP4 and 5 were highly induced in the ECs of Egln1 Tie2Cre mice and PAECs from IPAH patients, as well as the whole lungs of MCT and SuHx-induced PH rats. Knockdown or overexpression of FABP4-5 reduced or enhanced EC proliferation, starvation-induced Caspase 3/7 activity, glycolysis and fatty acid oxidation. Genetic deletion of Fabp4 and 5 in Egln1 Tie2Cre mice exhibited a reduction of right ventricular systolic pressure (RVSP), RV hypertrophy, and attenuation of pulmonary vascular remodeling, prevention of right heart failure. Fabp4-5 deletion also normalized EC glycolysis gene programming, reduced HIF-2a expression and endothelial proliferation in Egln1 Tie2Cre mice. Conclusions: FABP4 and 5 control EC glycolysis and contribute to the development of severe PH.
Abstract 12865: Is Atrial Fibrillation in HFpEF a Distinct Endotype? Insights From Multiparametric MRI and Circulating Fibroinflammatory Markers
Authors: Abhishek Dattani, Prathap Kanagala, Kelly S Parke, Anna-Marie Marsh, Emer M Brady, Anvesha Singh, Jayanth R Arnold, Alastair J Moss, Iain B Squire, Leong L Ng, Gaurav S Gulsin, Gerry P McCann
Journal: Circulation (2022)

Introduction: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently occur in parallel. Whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics is not known. Methods: Adults with heart failure with an LV EF greater than 50% on echocardiography were prospectively recruited as part of the DIAMOND HFpEF study (NCT03050593). Participants underwent phenotyping including a panel of 49 fibroinflammatory plasma biomarkers, echocardiography and comprehensive stress cardiac MRI (CMR). Between group comparisons were adjusted for age, sex, ethnicity, body mass index (BMI), diabetes, systolic blood pressure and estimated glomerular filtration rate (eGFR). Results: 136 participants were included: sinus rhythm (n=75) and AF (n=61). Patients with AF were older (76 vs. 70 years), less ethnically diverse (minority ethnicity 7 vs. 24%) and had a lower prevalence of diabetes (36 vs. 61%). There were no significant differences in heart rate, blood pressure, BMI, eGFR, HbA1c, E/e’ or B-type natriuretic peptide, but AF patients had higher NTproANP (7704 vs. 5749pg/mL) and shorter E deceleration time (211±60 vs. 259±78ms). On CMR, ventricular volumes, mass, stress myocardial blood flow and myocardial fibrosis were similar, but those in AF had increased atrial volume (61±30 vs. 39±15mL/m 2 ), reduced systolic function (LV EF 63±8 vs. 68±8%; global longitudinal strain 13.6±2.9 vs. 14.7±2.4%, p=0.003) but higher diastolic strain rate (0.73±0.28 vs. 0.53±0.17/s, p&lt;0.001). Patients with AF had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP and angiopoietin-2, but lower level of interleukin-8 (p&lt;0.05 for all; Figure 1). Conclusions: In HFpEF, AF is associated with lower systolic function but higher diastolic strain rate and a different fibroinflammatory profile compared to sinus rhythm. These findings may suggest that some patients with AF and HFpEF have a distinct endotype.